RdRp is an essential protein encoded in the genomes of most RNA-containing viruses that lack a DNA stage,[1][2] including SARS-CoV-2.

[13] During the following elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product.

[15] Viral/prokaryotic RdRp, along with many single-subunit DdRp, employ a fold whose organization has been linked to the shape of a right hand with three subdomains termed fingers, palm, and thumb.

The asparagine residue of motif B is involved in selection of ribonucleoside triphosphates over dNTPs and, thus, determines whether RNA rather than DNA is synthesized.

[17] The domain organization[18] and the 3D structure of the catalytic centre of a wide range of RdRps, even those with a low overall sequence homology, are conserved.

Unlike the "hand" polymerases, they resemble simplified multi-subunit DdRPs, specifically in the catalytic β/β' subunits, in that they use two sets of double-psi β-barrels in the active site.

[20] Bacteriophage homologs of c RdRp, including the similarly single-chain DdRp yonO (O31945), appear to be closer to c RdRps than DdRPs are.

Recombination appears to occur by a copy choice mechanism in which the RdRp switches (+)ssRNA templates during negative strand synthesis.

[32] This positive L–L interaction is referred to as intragenic complementation and indicates that the L protein is an oligomer in the viral RNA polymerase complex.

[citation needed] The use of RdRp plays a major role in RNA interference in eukaryotes, a process used to silence gene expression via small interfering RNAs (siRNAs) binding to mRNA rendering them inactive.

[36] Eukaryotic RdRp becomes active in the presence of dsRNA, and is less widely distributed than other RNAi components as it lost in some animals, though still found in C. elegans, P. tetraurelia,[37] and plants.

[38] This presence of dsRNA triggers the activation of RdRp and RNAi processes by priming the initiation of RNA transcription through the introduction of siRNAs.